The proposed research is concerned with identifying the factors that cause irreversible damage to oxygen-deficient myocardium when oxygen deficiency is associated with various states such as normothermic, contracting tissue made hypoxic and ischemic, hypothermic hypoxic and ischemic states and hypothermic arrested hearts where coronary flow is maintained at various rates. Many of these conditions will provide information on the best procedure for preserving cardiac integrity durig open heart surgical procedures. The hypothesis to be tested is that simple oxygen deficiency does not cause irreversible damage to the heart, but that accumulation of metabolic products, inhibition of metabolic pathways, destruction and/or distortion of cellular membranes due to binding of accumulated lipid active products of metabolism and loss of key enzymes, cofactors and metabolites that occur secondarily to oxygen deficiency are responsible for irreversible damage. Some of these destructive processes can be prevented or slowed by various procedures such as preservation of cellular adenine nucleotides by cardiac arrest and hypothermia. A second portion of the study is concerned with improved techniques for inducing oxygen deficiency and for preperfusion or reoxygenation of ischemic and/or hypoxic hearts. These studies will concentrate on prevention and reversal of the secondary biochemical alterations that are associated with oxygen deficiency, primarily the accumulation of metabolic products.